Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Stereospecific Assembly of Fused Imidazolidines via Tandem Ring Opening/Oxidative Amination of Aziridines with Cyclic Secondary Amines Using Photoredox Catalysis Murugan Vijay,† Sundaravel Vivek Kumar,† Vanaparthi Satheesh,† Periyasamy Ananthappan,‡ Hemant Kumar Srivastava,† Sundaram Ellairaja,‡ Vairathevar Sivasamy Vasantha,‡ and Tharmalingam Punniyamurthy*,† Downloaded via NOTTINGHAM TRENT UNIV on September 6, 2019 at 01:43:52 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
†
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India School of Chemistry, Madurai Kamaraj University, Madurai 625001, India
‡
S Supporting Information *
ABSTRACT: Sustainable assembly of imidazolidines is accomplished via a sequential stereospecific ring opening and C−H amination using aziridines with secondary cyclic amines under visible light mediated indazoloquinoline photoredox catalysis at ambient conditions. Optically active aziridines are coupled with high enantiomeric purities. The computational studies provide insights on the redox properties of the catalysts as well as a profile of the reaction.
V
Scheme 1. Outline of this Work
isible-light photoredox catalysis affords a powerful synthetic tool for the sustainable construction of carbon−carbon and carbon−heteroatom bonds.1 In particular, organo photoredox catalysis is a vibrant field, providing an effective synthetic strategy for the conversion of the simple substrates into complex molecules with structural diversity.2 Ideally, these catalysts are attractive, as they are cheap, are less toxic, and have comparable redox potential as that of the metal-based systems.3 However, synthetic application of the organic dyes is still fairly limited, as few catalyst choices are available. Development of organic photoredox catalysts with broad redox competencies is thus valuable.4,5 Indazoloquinolines (IQ) are widely utilized as the organic light emitting diodes (OLED).6 These robust fluorescent frameworks can offer a unique stance to alter the redox properties by installing diverse functional groups. In addition, fused imidazolines are often found in natural products and bioactive compounds.7 Efforts are thus made on the development of synthetic methods to construct these scaffolds.8 Recently, Seidel and coworkers reported a benzoic acid catalyzed redox-neutral annulation of amine with ketoamides (Scheme 1a),8f while Meggers and co-workers demonstrated a chiral Ru-catalyzed C−N cyclization of tetrahydroisoquinoline with 2-azidoacetamides with up to 92% ee (Scheme 1b).8g Herein, we present a stereospecific assembly of imidazolidines via a tandem ring opening and an oxidative amination of aziridines with cyclic secondary amines utilizing quinoline based IQ-A-E photoredox © XXXX American Chemical Society
catalysts in visible light (Scheme 1c). Optically active aziridines can be reacted with 94−99% ee. Computational studies (DFT and TD-DFT) afford insight of the redox properties of the catalysts. To the best of our knowledge, this is the first example available using IQ photoredox catalysis. Rh-catalyzed regioselective C−H functionalization of 2-aryl2H-indazoles with alkynes produced indazoloquinolines IQ-AReceived: August 19, 2019
A
DOI: 10.1021/acs.orglett.9b02957 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Table 1. Optimization of the Reaction Conditionsa,b
D and indazolonaphthyridine IQ-E in 56−74% yields (Figure 1). Upon visible light irradiation, IQ-A-E showed a nano-
entry
deviation
3a (%)
4a (%)
1 2 3 4 5 6 7 8 9 10
None IQ-A instead of IQ-D IQ-B instead of IQ-D IQ-C instead of IQ-D IQ-E instead of IQ-D Eosin Y instead of IQ-D Rose bengal instead of IQ-D Ru(bpy)3Cl2·6H2O instead of IQ-D Ir(ppy)3 instead of IQ-D Without IQ-D and light
86 69 61 72 55 40 46 n.d. n.d. n.d.
n.d. 10 19 12 31 45 33 87 85 88
a
Reaction conditions: 1a (0.30 mmol), 2a (0.25 mmol), [cat.] (3 mol %), DMF (2 mL), air, rt, 24 h. bIsolated yield. n.d. = not detected.
cyclization using the photoredox catalysis to furnish 3a as a single diastereomer via an oxidative amination. With the optimized conditions, the scope of the procedure was examined for the reaction of a series aziridines 2b−o using 1a as a standard substrate (Scheme 2). Modulation in the 2Figure 1. Redox potentials of IQ-A-E with the common catalysts (vs SCE, all potentials mentioned hereafter against SCE). Computed values are given in parentheses. For simplicity, only excited state redox potentials are shown. a 1H NMR shows a 10:1 inseparable mixture of rotomers. See SI for more details.
Scheme 2. Scope of Aziridinesa,b
second singlet excited state with the strong oxidative (E*redexp = +1.65 V to +1.85 V, vs SCE and E*redDFT = +1.41 V to +1.65 V, vs SCE) and reductive (E*oxexp = −1.73 V to −1.91 V, vs SCE and E*oxDFT = −2.15 V to −2.62 V, vs SCE) competencies that are comparable/superior to the common photoredox organic dyes and metal complexes (Figure 1 and SI). The electronic properties indicated that the HOMO− LUMO gap of IQ (ΔEopt = 2.84 to 2.90 eV, Egexp = 2.48 to 2.84 eV and ΔEDFT = 3.96 to 4.05 eV; see SI) can facilitate the formation of a radical through a single electron transfer (SET). This wide window of strong redox potentials suggests that IQA-E are most suitable to promote single electron transfer of organic molecules under visible light. Having the inspired redox results, we initiated the optimization studies for the reaction of tetrahydroisoquinoline 1a with 2-phenyl-1-tosylaziridine 2a as the test substrates to examine the feasibility of the hypothesis that can lead to diverse fused imidazolidines (Table 1 and SI: Tables S1 and S2). To our delight, the reaction occurred to produce 3a in 86% yield when the substrates were stirred with 3 mol % IQ-D for 24 h in DMF under white LED 14 W irradiation (entry 1). The reaction of IQ-A-C gave 61−72% yields, while IQ-E furnished a 55% yield along with 4a in 98% ee (Scheme 6). The absolute configuration was determined using the single crystal X-ray analysis of (R,S)-3a′. These results posited the initial ring opening of the aziridine with amine takes place via the stereospecific pathway.10 To gain insight in the mechanism, a series of control experiments and theoretical studies were performed. Amine 1a underwent reaction with 2a to give 4a in quantitative yield, which showed no cyclization in the absence of the photoredox catalyst. In addition, the compound 4a underwent C−H amination to give 3a in 91% yield using IQ-D*, which suggests that the reaction involves a tandem ring opening and oxidative amination using photoredox catalysis (see SI). The Stern− Volmer quenching studies posited that the electron transfer occurs at 4a to IQ-D* (see SI). An alternative pathway, proceeding via the electron transfer from 1a to IQ-D*, leads to the formation of 3,4-dihydroisoquinoline and light-mediated
a
Reaction conditions: Amine 1b−m (0.30 mmol), aziridines 2a (0.25 mmol), IQ-D (3 mol %), DMF (2 mL), white LED 14 W, rt, air. b Isolated yield. cCalculated using 1H NMR. C
DOI: 10.1021/acs.orglett.9b02957 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
cyclization of c can lead to the formation of the target compound 3. Formation of the single diastereomer suggests that the cyclization can take place via the transition state TS c compared to that of TS d, which can be attributed to the 1,3diaxial interaction. The proposed reaction pathway was further examined by computational studies using M06/6-31+G(d,p) (see SI). The reaction of 1a with 2a can produce 4 through the TS-1 with an activation barrier of 37.30 kcal/mol (Figure 2). Formation of 4 is favored, as the stabilization is much more than the activation barrier. When the relative stability of 4 was compared with 4′, 4′ is around 2 kcal/mol less stable than 4, and thus the formation of 4′ is ruled out. SET from the catalyst to 4 can give a, which is 2.80 kcal/mol more stable than 4. Interaction of O2•− with a through TS-2 can form b, and this step is the rate-determining step as the barrier for the formation is highest (38.55 kcal/mol). This finding is in accordance with the observed experimental results. The abstraction of a proton from b can form c through TS-3, which is a quick reaction with the barrier of 1.55 kcal/mol and the stabilization of more than 12 kcal/mol. Cyclization of c can lead to the target 3, which is very fast, as the activation barrier TS-4 is less than 1 kcal/mol. The relative stability of 3 and 3′ were compared to prove that the formation of 3 is favored over 3′. Finally, the scale-up (1 mmol) of the procedure was studied using 1a with 2a as the representative substrates (Scheme 7). The reaction occurred to give the target heterocycle 3a in 79% yield.
Scheme 6. Proposed Mechanism and Stereochemical Model
ring opening of aziridine, which is unlikely because no quenching was observed at IQ-D* by 1a or 2a. Next, we measured the oxidation potential, Eoxexp = 0.92 to 1.05 V and EoxDFT = +1.14 to +1.26 V, for a series of electronically varied intermediates 4a, 4j−k, and 4p−q as the representative examples, which suggest that they can be oxidized by the excited IQ-D* E*redexp = +1.72 V and E*redDFT = +1.52 V (see SI). In addition, the reaction generates H2O2, which was confirmed using the iodide test (KI in acetic acid) which suggests that O2 plays an important role in the catalysis (see SI). Further, the one-pot ([PH/PD] = 3.3) and parallel (kH/kD = 4.3) kinetic isotope experiments suggest that the hydrogen atom transfer (HAT) can be the rate-determining step (see SI). These experimental results and literature reports1,2 suggest that the stereospecific ring opening of aziridine 2 with 1 can produce 4 with an inverted stereochemistry (Scheme 5). The visible light irradiation of IQ-D can produce the excited IQD*, which can undergo single electron transfer (SET) with 4 to afford the radical cation a and radical anion IQ-D•−. The latter can react with oxygen (air) to generate IQ-D and O2•− via the SET. Hydrogen atom transfer (HAT) from the radical cation a to O2•− can yield HO2− and imine b. HO2− mediated
Scheme 7. Scale-up Reaction
In conclusion, the stereospecific assembly of fused imidazolines is developed from N-sulfonyl aziridines and secondary cyclic amines via a tandem ring opening/C−H amination using
Figure 2. Calculated energy profile of tandem ring opening/C−H amination reaction at M06/6-31+G(d,p) level of theory. “Numbers in blue colors” depict the relative energies (kcal/mol), “numbers in bold” show the activation barrier, and “numbers in italics” show the stabilization. All energy values are given in kcal/mol. Important interatomic distances in transition state structures are given in green color in Å unit. Red color numbers and cross sign (X) show the unfavored intermediate or product. D
DOI: 10.1021/acs.orglett.9b02957 Org. Lett. XXXX, XXX, XXX−XXX
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visible IQ photoredox catalysis. The redox properties of the IQs have been demonstrated using DFT and TD-DFT studies.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b02957. Experimental procedure, crystal data, characterization data, and NMR spectra (1H, 13C, and 19F) of the products (PDF) Accession Codes
CCDC 1937814 and 1937816 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Sundaravel Vivek Kumar: 0000-0002-8054-730X Hemant Kumar Srivastava: 0000-0001-6589-6854 Vairathevar Sivasamy Vasantha: 0000-0001-8391-8682 Tharmalingam Punniyamurthy: 0000-0003-4696-8896 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank Science and Engineering Research Board (SERB) for the research grant (CRG/2018/000406) to T.P., National Postdoctoral Fellowship (PDF/2016/001460) to S.V.K., and Ramanujan Grant (DST-SERB SB/S2/RJN-004/2015) to H.K.S. We thank Dr. S. C. Pan, IIT Guwahati for the HPLC facility.
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REFERENCES
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